A variety of systems for identifying and classifying lymphomas have been proposed over the last 20 years. In the 1980's, the Working Formulation was introduced as a method of classifying lymphomas based on morphological and clinical characteristics. In the 1990's, the Revised European-American Lymphoma (REAL) system was introduced in an attempt to take into account immunophenotypic and genetic characteristics in classifying lymphomas (Harris 1994). The most recent standard, set forth by the World Health Organization (WHO), attempts to build on these previous systems (Jaffe 2001). The WHO classification of lymphomas is based on several factors, including tumor morphology, immunophenotype, recurrent genetic abnormalities, and clinical features. Table 1, below, contains a list of the B and T cell neoplasms that have been recognized by the WHO classification. Each malignancy is listed according to its WHO classification nomenclature, followed by a WHO classification number.
TABLE 1CategoryNameWHO ID #B-cell neoplasmsPrecursor B-cellPrecursor B-cell lymphoblastic9835/3neoplasmsleukemiaPrecursor B-cell lymphoblastic9728/3lymphomaMature B-cellChronic lymphocytic leukemia9823/3neoplasmsSmall lymphocytic lymphoma9670/3B-cell prolymphocytic leukemia9833/3Lymphoplasmacytic lymphoma9671/3Splenic marginal zone9689/3lymphomaHairy cell leukemia9940/3Plasma cell myeloma9732/3Solitary plasmacytoma of bone9731/3Extraosseous plasmacytoma9734/3Extranodal marginal zone B-cell9699/3lymphoma of mucosa-associated lymphoid tissue(MALT lymphoma)Nodal marginal zone B-cell9699/3lymphomaFollicular lymphoma (Grade 1,9690/32, 3a, 3b)Mantle cell lymphoma9673/3Diffuse large B-cell lymphoma9680/3Mediastinal (thymio) large B-cell9679/3lymphomaIntravascular large B-cell9680/3lymphomaPrimary effusion lymphoma9678/3Burkitt lymphoma9687/3Burkitt leukemia9826/3B-cell proliferations ofLymphomatoid granulomatosis9766/1uncertain malignantpotentialPost-transplant9970/1lymphoproliferative disorder,polymorphicT-cell and NK-cell neoplasmsPrecursor T-cell andPrecursor T lymphoblastic9837/3NK-cell neoplasmsleukemiaPrecursor T lymphoblastic9729/3lymphomaBlastic NK-cell lymphoma9727/3Mature T-cell andT-cell prolymphocytic leukemia9834/3NK-cell neoplasmsT-cell large granular9831/3lymphocytic leukemiaAggressive NK-cell leukemia9948/3Adult T-cell leukemia/lymphoma9827/3Extranodal NK-/T-cell9719/3lymphoma, nasal typeEnteropathy-type T-cell9717/3lymphomaHepatosplenic T-cell lymphoma9716/3Subcutaneous panniculitis-like9708/3T-cell lymphomaMycosis fungoides9700/3Sezary syndrome (9701/3)9701/3Primary cutaneous anaplastic9718/3large cell lymphoma (C-ALCL)Peripheral T-cell lymphoma,9702/3unspecifiedAngioimmunoblastic T-cell9705/3lymphomaAnaplastic large cell lymphoma9714/3T-cell proliferation ofLymphomatoid papulosis9718/3uncertain malignantpotentialHodgkin lymphomaNodular lymphocyte9659/3predominant HodgkinlymphomaClassical Hodgkin lymphoma9650/3Classical Hodgkin lymphoma,9663/3nodular sclerosisClassical Hodgkin lymphoma,9651/3lymphocyte-richClassical Hodgkin lymphoma,9652/3mixed cellularityClassical Hodgkin lymphoma,9653/3lymphocyte depletedOther diagnoses that have not been given WHO diagnostic numbers include HIV-associated lymphoma, germinal center B cell-like subtype of diffuse large B cell lymphoma, activated B cell-like subtype of diffuse large B-cell lymphoma, follicular hyperplasia (non-malignant), and infectious mononucleosis (non-malignant).
Although the WHO classification has proven useful in patient management and treatment, patients assigned to the same WHO diagnostic category often have noticeably different clinical outcomes. In many cases, these different outcomes appear to be due to molecular differences between tumors that cannot be readily observed by analyzing tumor morphology. More precise methods are needed for identifying and classifying lymphomas based on their molecular characteristics.